Clinical analysis of families with heart, midline, and laterality defects

Disturbances of the normal asymmetric placement of organs, such as polysple nia or situs inversus, have been defined traditionally as laterality defect s. However, there is compelling evidence from vertebrate models and human b irth defects to hypothesize that defects of the midline, isolated congenita l heart defects, and laterality defects are etiologically related. We prese nt the clinical characteristics of three families that exhibit a variety of midline defects and isolated heart defects in addition to laterality defec ts. These observations suggest that the phenotypic consequences of mutation s causing laterality defects include defects of the midline as well as isol ated heart defects. To further explore the relationship between midline, he art, and laterality defects, it is imperative that detailed phenotyping of individuals and families with laterality defects be done and a classificati on system created to facilitate identification of genes causing human later ality disorders. (C) 2001 Wiley-Liss, Inc.